Case report: Cryoablation as a novel bridging strategy prior to CAR-T cell therapy for B cell malignancies with bulky disease

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a powerful immunotherapy in relapsed/refractory (R/R) hematological malignancies, especially in R/R B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). To prevent disease progression and reduce tumor burden during CAR-T cell manufacturing, bridging therapies prior to CAR-T cell infusion are crucial. At present, it has been demonstrated that targeted therapy, radiotherapy and autologous stem cell transplantation (ASCT) could serve as effective bridging strategies. However, whether cryoablation could serve as a novel bridging strategy is unknown. In this paper, we report 2 cases of R/R B cell malignancies with bulky disease that were successfully treated with a combination of cryoablation and CAR-T cell therapy. Patient 1 was a 65-year-old female who was diagnosed with R/R MM with extramedullary disease (EMD). She was enrolled in the anti-BCMA CAR-T cell clinical trial. Patient 2 was a 70-year-old man who presented with a subcutaneous mass in the right anterior thigh and was diagnosed with primary cutaneous diffuse large B cell lymphoma, leg type (PCLBCL-LT) 1 year ago. He failed multiline chemotherapies as well as radiotherapy. Thus, he requested anti-CD19 CAR-T cell therapy. Unfortunately, they all experienced local progression during CAR-T cell manufacturing. To rapidly achieve local tumor control and reduce tumor burden, they both received cryoablation as a bridging therapy. Patient 1 achieved a very good partial response (VGPR) 1 month after CAR-T cell infusion, and patient 2 achieved a partial response (PR) 1 month after CAR-T cell infusion. In addition, adverse effects were tolerable and manageable. Our study demonstrated the favorable safety and efficacy of combination therapy with cryoablation and CAR-T cell therapy for the first time, and it also indicates that cryoablation could serve as a novel therapeutic strategy for local tumor control in B cell malignancies.

CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies

“…In addition, localized radiotherapy and cryoablation are effective bridging therapies for R/R MM patients with bulky mass. Localized radiotherapy and cryoablation in combination with anti-BCMA CAR-T cell therapy may result in synergistic anti-tumor effect ( 119 , 120 ). On the one hand, radiotherapy and cryoablation could directly destroy tumor cells; On the other hand, they could sensitize CAR-T cells and activate endogenous effector T cells through the abscopal effect, which may be associated with the upregulation of intratumoral chemokines and cytokines and the release of neo-antigens ( 119 – 121 ).…”

Nontuberculous mycobacterial infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation

“…Mycobacterial infections, caused by both Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), are increasingly recognized as significant contributors of morbidity and mortality among patients with hematologic malignancies and recipients of hematopoietic stem cell transplant (HSCT). Mycobacterial infections in patients following chimeric antigen cell therapies (CAR‐T) appear to less common 1–4 . Nonetheless, accurately estimating the risk of NTM infections in this patient population can be challenging, as it is likely affected by a combination of prior immunosuppressive therapies and the management of CAR‐T complications, including cytokine release syndrome (CRS) treatments involving high‐dose steroids and IL‐6 blockers 5 .…”

Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy

“…The focus has been on utilizing the patient’s immune system to find and destroy cancer cells with little or no harm to the healthy ones. Recently several immunotherapy strategies have been developed, such as immune checkpoint inhibitors, Anti-CTLA-4 antibodies, Anti-PD-1 drugs, and Anti-PD-L-1 drugs [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ], chimeric antigen receptor T-cells, or CAR-T [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”